Familial aggregation of depression in fibromyalgia: a community-based test of alternate hypotheses Karen G. Raphael a, * , Malvin N. Janal a , Sangeetha Nayak a , Joseph E. Schwartz b , Rollin M. Gallagher c,d a Department of Psychiatry, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, BHSB F1512, 183 S. Orange Avenue, Newark, NJ 07103, USA b Department of Psychiatry and Behavioral Science, Stony Brook University School of Medicine, Stony Brook, NY, USA c Pain Management Service, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA d Department of Psychiatry and Anesthesiology, University of Pennsylvania, Philadelphia, PA, USA Received 26 January 2004; received in revised form 24 March 2004; accepted 20 April 2004 Abstract Numerous studies report that fibromyalgia (FM), a syndrome characterized by widespread pain and generalized tender points, is comorbid with major depressive disorder (MDD). The current study tests two alternate explanations for their comorbidity using a family study methodology. The first is that FM is a depression spectrum disorder. The second is that depression is a consequence of living with FM. We recruited potential probands by initially screening by telephone for FM and MDD among women in the NY/NJ metropolitan area, randomly selecting telephone numbers from a list of households with women. Eligible women were invited for second stage physical examinations for FM diagnosis and psychiatric interviews for MDD diagnosis. All available adult, first-degree relatives received psychiatric interviews. Relatives of probands were divided into four groups on the basis of the probands’ FM and MDD diagnoses (FMþ /MDDþðn ¼ 156Þ; FMþ /MDD2 ðn ¼ 51Þ; FM2 /MDDþðn ¼ 351Þ and FM2 /MDD2 ðn ¼ 101Þ). Results indicated that rates of MDD in the relatives of probands with FM but without personal histories of MDD were virtually identical to rates of MDD in relatives of probands with MDD themselves. This outcome is consistent with the hypothesis that FM is a depression spectrum disorder, in which FM and MDD are characterized by shared, familially mediated risk factors. The implications of these findings for a stress-vulnerability model of FM are discussed. q 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Keywords: Fibromyalgia; Major depressive disorder; First-degree relatives The etiology of fibromyalgia (FM), a syndrome character- ized by widespread pain and generalized tender points, is still elusive. In addition to biological and genetic theories, many etiological hypotheses have focused on the potential role of psychosocial and psychiatric factors, since patients with FM often have a history of major depressive disorder (MDD). 1. Comorbidity of FM and MDD Numerous studies find that FM patients are at increased risk for a lifetime history of major depression (MDD). One review found rates ranging from 20 to 80% with a median rate of 58% (Hudson and Pope, 1996). While most critical reviews (e.g. Boissevain and McCain, 1991; Hudson and Pope, 1996) conclude that FM and MDD are related, controversy exists about the nature of the processes underlying the comorbidity. The current investigation tests two alternate explanations for their association. 1.1. Hypothesis 1: FM is a depression spectrum disorder Variations on the assertion that psychosocial factors are prominent in the pathogenesis of FM dates back to the 1940s (Ellman et al., 1942). This includes the concept of pain disorders of unknown origin as ‘masked depression’ (Blumer and Heilbronn, 1982) or the more tempered 0304-3959/$20.00 q 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2004.04.039 Pain 110 (2004) 449–460 www.elsevier.com/locate/pain * Corresponding author. Tel.: þ 1-973-972-5462; fax: þ1-973-972-8305. E-mail address: raphaekg@umdnj.edu (K.G. Raphael).